Three Gene Cell Cycle/Cancer Model

In this activity, we will work with the two groups of genes that control the cell cycle, proto-oncogenes and tumor suppressor genes. We will also add a new group of genes that are in charge of the maintenance of our DNA, the DNA repair system. Every cell's DNA is under constant attack from chemicals or radiation they are exposed to in the environment as well as chemicals that are the result of their own chemical reactions. DNA even becomes damaged during replication (more detail about DNA damage). The DNA repair system detects and repairs the errors in the DNA. However, there is a chance that the genes that are involved in the DNA repair system may get damaged themselves. This can lead to an increase in the mutation rate for that cell and a greater possibility that you will accumulate the mutations needed to cause cancer. For this activity, we will assume that we are focusing in on our own skin cells.

Remember:

Proto-oncogenes are like the gas pedal of the cell cycle. They produce proteins that signal a cell to divide. Some cells divide often (those found in an embryo or a wound healing) and would use this gene frequently, while others divide less frequently or not at all (muscle cell, neuron). If this gene were to mutate in such a way that it continually signals a cell to divide and we start accumulating too many cells, it is now an oncogene, and could be thought of as a gas pedal stuck in the down position.

Tumor Suppressor Genes are like the brake pedal of the cell cycle. When DNA is damaged, the tumor suppressor gene stops the cell cycle so that repairs can be made. If the damage is beyond repair, it will signal the cell to commit suicide, apoptosis. This prevents the replication of cells with mutated DNA or cells that do not have a complete set of functioning genes, which are needed to maintain healthy cells. Cells die every day and go unnoticed. We have probably all experienced massive apoptosis or cell suicide however, when our skin peels following sunburn.

Step 1: Cell Cycle Model with Students Acting as the Genes that Control the Cycle

(This activity is done as a skit in front of the class to introduce new genes as well as review the students understanding of genes they have worked with previously. In this activity, we will introduce the students to the genes involved in the DNA repair system or the genes in charge of maintenance. They will also work with the genes from the previous activity, proto-oncogenes and tumor suppressor genes, as they apply what they know to this new situation involving the interaction of more than one gene to produce a phenotype.)

Who: One student will represent each of the following groups of genes (Wear signs or hat with the name of the group of genes they represent). Proto-oncogenes, tumor suppressor genes, DNA repair system, DNA synthesis system. The teacher or group leader will act as UV Radiation when needed.

What: They will model the Cell Cycle.

Where: They will represent the genes in a skin cell at the base of the stratified squamous tissue that is going through its cell cycle.

When: Summer Vacation.

Why: The cell needs to replace cells that are lost during the normal activity of this person.

How: That is the job of each of these groups of genes working together. See their job descriptions below.

Proto-oncogenes

  • Gas pedal of the cell cycle
  • Produce protein that signals a cell to divide (hold up "Divide" sign)

DNA Synthesis System

  • Duplicate DNA so we have two sets of DNA when the cell divides (copy message decided by teachers onto card in 5 seconds with pencil)

Tumor Suppressor Genes

  • Brake pedal of cell cycle
  • When DNA is damaged you stop the cell cycle to allow for repairs (hold up stop sign)
  • If beyond repair (DNA repair system can't repair in 5 seconds) - signal cell to commit suicide (hold up apoptosis sign)
  • If it is repaired (in 5 sec) the cell continues cycle (hold up GO sign)
  • Prevents the replication of cells with damaged DNA

DNA repair system

  • Maintenance for cell cycle
  • Every cell's DNA is under constant attack - chemicals, radiation, chemicals from own reactions (free radicals)
  • Detects and repairs errors - even oncogenes and Tumor Suppressors (use eraser and pencil and repair within 5 sec.)

PROCEDURE FOR SKIT

  1. Students representing each group of genes will line up in the front of the room wearing their signs for easy identification. Run through a normal cell cycle with all genes functioning normally.
    1. Proto-oncogene holds up the "divide" sign telling the cell to prepare for division.
    2. DNA Synthesis System duplicates the DNA by copying the message on the DNA card onto another card so the cell has two complete sets of DNA (two identical cards)
    3. Tumor Suppressor Gene checks the DNA and only stops the cell cycle (holds up STOP sign) if there is an error and the cell needs time to repair it.
    4. DNA Repair System does nothing unless the Tumor Suppressor has stopped the cell cycle. It then repairs the DNA by correcting the message on the card.
    5. If there is not enough time for repair the tumor suppressor cell will instruct the cell to commit suicide (apoptosis).
    6. At the end of the normal cell cycle you should have two copies of identical DNA that represent the two cells resulting from the cell division.
  2. Mutate the proto-oncogene changing into an oncogene. To do this you can shine a flashlight (represents UV light) on the student who is representing the proto-oncogenes and say that you have mutated this gene turning it into an oncogene. Cover up the word "proto" on their sign with blank paper and put the word "STUCK" in front of "Gas Peddle". An oncogene functions like a stuck gas pedal in the down position. The cell will continually get the signal to divide from this gene. Run the cell cycle to see how the result changes. The tumor suppressor gene still has the ability to stop the cycle for repairs by the maintenance system. The students should accumulate many more cells but the cell's DNA will be normal. This could represent the formation of a benign tumor.
  3. This time mutate only the Tumor Suppressor genes. Put a "NO" in front of "Brake Pedal" on their sign. This means that this group of genes can no longer detect DNA damage and the cells will not stop during the cell cycle for repair if damage has occurred during duplication or from mutations caused by an outside force such as UV light. To model this even further you can blindfold the student representing the tumor suppressor genes so they can't see what is written on the DNA cards. Run the cycle to see how the result changes. As cells accumulate, you may notice that some of them have mutated DNA that has not gotten repaired by the cell. As new cells accumulate, multiple mutations increase their chances of becoming a cancerous cell produced by a cell cycle out of control.
  4. These are examples of two possible mutations to run through this model. Now try other mutations as well as combinations of mutations that alter how the cell cycle genes function and see what the result might be for your skin cells on summer vacation.
When you feel that the students have a good understanding of how the genes function together let them practice applying their knowledge in the following activity.

Step 2: Making Predictions

Using your knowledge of how the cell cycle genes function, predict a possible outcome for your skin cells in each of the 8 combinations represented on the genetic wheel. Be sure to explain WHY you have arrived at this prediction. To use a genetic wheel, you begin in the middle and work out passing through each layer selecting different gene combinations as you go. Each of the 8 locations on the outside of the wheel represents a different combination of the three genes. For example, if you begin in the center and select "proto-oncogene" in the first circle, "tumor suppressor gene" in the second circle, and "DNA repair" in the third circle you have the combination of genes we started with. All genes are functioning normally and the outcome should be normal cells. As a second combination, you could start in the middle and select "oncogene" in the first circle, "tumor suppressor gene" in the second circle, and "DNA repair" in the third circle. This would be the combination we described in the skit that resulted in too many normal cells, representing a benign tumor in our model.

Work through a few combinations as a class or in groups to be sure you know how to use a genetic wheel. Work through the remaining combinations on the genetic wheel on your own as homework.

To see how scientists will be able to determine which genes are functioning in a given cell in your body, such as a tumor, go to Genetic Variation and check out the Microarray section.

Remember, this is just a simple model that allows you to see how genes work together to produce a final outcome. In reality, each of these genes represents groups of genes that work together, along with others not included here, to move our cells through their cell cycle. Also, all the mutations needed to cause cancer, must occur in the same cell and that is why it usually takes time for cancer to develop and why it appears later in life.